Epigenetic regulation by dietary metabolites

Microbial metabolism of dietary fibre produces short chain fatty acids (SCFAs) like butyrate and propionate, which have been shown to have health benefits by exerting anti-inflammatory effects and are associated with reduced CRC risk. These metabolites have been identified as unique acyl lysine histone marks.

The researchers show that SCFAs are conjugated inside cells to their respective acyl-CoA, which are substrates for histone acetyl transferase (HAT) enzymes. 

Histone deacetylase (HDAC) enzymes remove histone acetylation marks by liberating acetate. The authors show that  butyrate is a relatively strong HDAC inhibitor compared with propionate. 

The authors also demonstrate that propionate and butyrate bind and act as promoters of genes involved in growth, differentiation and ion transport.

In cancer cells, the researchers show overexpression of already high levels of proto-oncogenes controlling growth and differentiation, which may ultimately lead to cell death, especially in instances of elevated butyrate levels.

https://www.nature.com/articles/s42255-024-01191-9

https://sciencemission.com/Short-chain-fatty-acid-metabolites